Foscarnet salvage therapy efficacy is associated with the presence of thymidine-associated mutations (TAMs) in HIV-infected patients

BackgroundSalvage therapy based on foscarnet plus a thymidine analog is effective in patients with advanced-stage HIV disease and viruses harbouring multiple drug-resistance mutations.ObjectiveTo identify viral genetic determinants associated with the virological efficacy of foscarnet salvage therapy.Study designThirteen patients received foscarnet at a fixed dose of 80 mg/kg twice daily for 14 days, in combination with zidovudine or stavudine.ResultsThe baseline median HIV viral load and CD4 cell count were 5.10 log10 copies/ml and 23 cells/mm3, respectively. Following foscarnet therapy, viral load fell by a median of 1.84 log10 copies/ml (range: −0.29 to −2.82), and by at least 1 log10 copies/ml in 11 patients, all of whom harboured viruses with at least three thymidine-associated mutations (TAMs). The two patients with smaller declines in viral load (<0.50 log10 copies/ml) harboured viruses with only one or zero TAMs.ConclusionsThese findings corroborate, in vivo, the impact of TAMs on HIV susceptibility to foscarnet. The virological response to foscarnet salvage therapy in multiclass-experienced patients may thus differ according to the number of TAMs.